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Bone Markers Improve After Switch From TDF/FTC to ABC/3TC, While Dropping RTV
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52nd ICAAC, September 9-12, 2012, San Francisco
Mark Mascolini
Bone and kidney markers, and "good" high-density lipoprotein (HDL) cholesterol, all improved significantly in the 24 weeks after a switch from atazanavir/ritonavir plus tenofovir/emtricitabine (TDF/FTC) to unboosted atazanavir plus abacavir/lamivudine (ABC/3TC) in a randomized noninferiority trial [1]. Both regimens maintained virologic suppression after randomization.
Renal and bone side effects with tenofovir and ritonavir-related metabolic complications are well documented. Possible cardiovascular complications associated with abacavir remain controversial, but US Department of Health and Human Services antiretroviral guidelines no longer list ABC/3TC as a "preferred" first-line option [2]. These guidelines rate unboosted atazanavir as an "acceptable" regimen, one step below "alternative" regimens. The IAS Panel included abacavir as a recommended firstline therapy in guidelines issued at the IAC July 2012 in Wash DC [3].
ASSURE is an open-label noninferiority trial that recruited people with a viral load below 75 copies and an estimated creatine clearance at or above 50 mL/min while taking atazanavir/ritonavir plus TDF/FTC for at least 6 months. The primary endpoint was the proportion of people with a viral load below 50 copies at week 24 in a time-to-loss-of-virologic response (TLOVR) analysis. Researchers randomized participants in a 2-to-1 ratio to switch to unboosted atazanavir (400 mg daily) plus ABC/3TC or to stay with boosted atazanavir plus TDF/FTC.
Among 296 study participants who took at least one dose of study drugs, median age was 44 years, 79% were men, and 60% were white. Median pretreatment viral load stood below 40 copies, and median CD4 count was 492. Of the 296 treatment-exposed participants, 19 (10%) withdrew from the ABC/3TC switch arm and 9 (9%) from the TDF/FTC maintenance arm. Adverse events accounted for 7 withdrawals (4%) in the switch arm and 2 (2%) in the maintenance arm. Lack of efficacy accounted for a single withdrawal--in the ABC/3TC arm.
At the 24-week point, 173 of 199 people randomized to switch to ABC/3TC and 84 of 97 who stayed with TDF/FTC maintained an undetectable viral load in the TLOVR analysis (86.9% versus 86.6%, P = 0.937). There were 6 virologic failures (3%) in the ABC/3TC group and 1 (1%) in the TDF/FTC group..
Mean CD4 count rose by 37 in the group that switched to ABC/3TC and hardly changed in the group that stayed with TDF/FTC. But David Wohl (University of North Carolina), who presented the results, cautioned that further follow-up is needed before CD4 results can be interpreted.
Rates of any grade 2 to 4 adverse events were 40% in the ABC/3TC group and 37% in the TDF/FTC group. When the researchers assessed emergent or worsening lab toxicities affecting at least 5% of participants, the overall rate was lower in with ABC/3TC than TDF/FTC (38% versus 60%). High bilirubin accounted for most of that difference (16% versus 47%).
Several bone and renal markers--bone alkaline phosphatase, c-telopeptide, osteocalcin, and parathyroid hormone--fell significantly (P < 0.001) from baseline measures in people who switched to ABC/3TC but not in those who stayed with TDF/FTC. The overall difference between groups was also statistically significant (P < 0.001). Among lipid values, "good" HDL cholesterol rose significantly by 4 mg/dL in the switch group (P < 0.001) but did not change in the control group. Markers of inflammation and clotting--high-sensitivity C-reactive protein, interleukin 6, and d-dimer--did not change significantly in either treatment arm.
References
1. Wohl D, Bhatti L, Small CB, et al. Simplification to abacavir/lamivudine + atazanavir from tenofovir/emtricitabine + ATV/ritonavir maintains viral suppression and improves bone biomarkers. 52nd Interscience Conference on Antimicrobials and Chemotherapy (ICAAC). September 9-12, 2012. San Francisco. Abstract H-556c.
2. HHS Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. March 28, 2012.
3. Antiretroviral Treatment of Adult HIV Infection2012 Recommendations of the International Antiviral Society-USA Panel - (07/25/12)
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